J. van der Meer

Reduced transfusion requirements by recombinant factor VIIa in orthotopic liver transplantation : A pilot study

Background. Large transfusion requirements, i.e., excessive blood loss, during orthotopic liver transplantation (OLT) are correlated with increased morbidity and mortality. Recombinant factor VIIa (rFVIIa) has been shown to improve hemostasis in a variety of conditions, but has never been studied in liver transplantation. Methods. We performed a single-center, open-label, pilot study in adult patients undergoing OLT for cirrhosis Child-Pugh B or C, to assess efficacy and safety of rFVIIa. rFVIIa (80 &mgr;g/kg) was administered at the start of the operation, to be repeated according to predefined criteria. Packed red blood cells (RBC), fresh-frozen plasma, and platelet concentrates were administered according to predefined criteria. Perioperative transfusion requirements in study patients were compared with matched controls. Results. Six patients were enrolled in the study. All received a single dose of rFVIIa. Transfusion requirements (given as median, with range in parentheses) were lower in the study group than in matched controls: 1.5 (0–5) vs. 7 (2–18) units of allogeneic RBC (P =0.006), 0 (0–2) vs. 3.5 (0–23) units of autologous RBC (P =0.043), total amount of RBC 3 (0–5) vs. 9 (4–40) units (P =0.002). Transfused fresh-frozen plasma was 1 (0–7) vs. 8 (2–35) units (P =0.011). Blood loss was 3.5 L (1.4–5.3) vs. 9.8 L (3.7–35.0) (P =0.004). One study patient developed a hepatic artery thrombosis at day 1 postoperatively. Conclusions. A single dose of 80 &mgr;g/kg rFVIIa significantly reduced transfusion requirements during OLT. Further study is needed to establish the optimally effective and safe dose of rFVIIa in orthotopic liver transplantation.

Is extensive screening for cancer in idiopathic venous thromboembolism warranted

Summary.u2002 Background:u2002Patients with a first episode of idiopathic venous thromboembolism (IVTE) have an estimated 10% incidence of cancer within 12u2003months after diagnosis. However, the utility of screening for cancer in this population is controversial. Methods:u2002In this prospective concurrently controlled cohort study, limited and extensive cancer screening strategies were compared. All 630 patients underwent baseline screening consisting of history, physical examination, basic laboratory tests and chest X‐ray. In the extensive screening group abdominal and chest CT scan and mammography were added. Outcomes were incidence and curability of cancer, and cancer‐related and overall mortality. Results:u2002In 12 of the 342 (3.5%) patients in the extensive screening group malignancy was diagnosed at baseline compared with 2.4% (seven of 288 patients) in the limited screening group. Extensive screening detected six additional cancers (2.0%; 95% CI, 0.74–4.3), of which three were potentially curable. During a median 2.5u2003years of follow‐up, cancer was diagnosed in 3.7% and 5.0% in the extensive and limited screening groups, respectively. In the extensive screening group 26 patients (7.6%) died compared with 24 (8.3%) in the limited screening group; adjusted hazard ratio 1.22 (95% CI, 0.69–2.22). Of these deaths 17 (5.0%) in the extensive screening group and 8 (2.8%) in the limited screening group were cancer related; adjusted hazard ratio 1.79 (95% CI, 0.74–4.35). Conclusions:u2002The low yield of extensive screening and lack of survival benefit do not support routine screening for cancer with abdominal and chest CT scan and mammography in patients with a first episode of IVTE.

Prevention of primary cytomegalovirus infection after allogeneic bone marrow transplantation by using leukocyte-poor random blood products from cytomegalovirus-unscreened blood-bank donors

Cytomegalovirus infection was studied in 59 seronegative recipients of bone marrow depleted of lymphocytes by counterflow centrifugation. Eighteen patients died within 3 months after bone marrow transplantation without evidence of CMV infection, and they were excluded from analysis. Twenty-eight valuable seronegative patients received marrow from a seronegative donor, and 13 from a seropositive donor. All but 2 patients received acyclovir orally (4 x 400 mg/day) from days -9 to +60. CMV prophylaxis with immunoglobulin preparations was not given. All blood products were prepared from random, CMV-unscreened blood-bank donors. The red cell concentrates were depleted of leukocytes by filtration, and leukocytes were removed from the platelet concentrates by centrifugation. None of the patients with seronegative donors showed any clinical sign compatible with CMV infection. Two nonfatal primary CMV infections occurred in the recipients of bone marrow from CMV-positive donors. One of the 59 patients developed interstitial pneumonia, in this case caused by Pneumocystis carinii. Leukocyte depletion of blood products from random CMV-unselected blood donors appeared to prevent primary infection in CMV-seronegative BMT recipients. We conclude that prophylactic use of immunoglobulin preparations is not necessary to prevent CMV primo-infection in patients receiving leukocyte-depleted blood products and acyclovir prophylaxis during the first 2 months postgrafting.

Protein S deficiency: a clinical perspective

Summary.u2002 Protein S (PS) is an extensively studied protein with an important function in the down‐regulation of thrombin generation. Because of the presence of a pseudogene and two different forms of PS in plasma, a bound and a free form, it is one of the most difficult thrombophilias to study. A deficiency of PS predisposes subjects to (recurrent) venous thromboembolism (VTE) and foetal loss. However, the conundrum of diagnosing PS deficiency has led to conflicting reports of PS as a risk factor for VTE. In this review, we aim to present a clinical perspective of PS deficiency.

High rate of skin complications due to low-molecular-weight heparins in pregnant women

t I^ow-molecularr weight heparins (LMWH) arc widely used in patients in whom anticoagulantt therapy is indicated and skin complications are considered to be rare. . Off 66 consecutive pregnant or postpartum women seen, 29% developed skin complicationss while receiving LMWH . Almost one-fourt h had to switch to another preparationn because of these side elfects, which mainly constituted of delaved hypersensitivit yy reactions and itching. Former use of L M W H and protein C deficiencyy predispose d to skincomplications . Incase of sever e skin complications necessitatin gg discontinuation, another LMW H is tolerated by approximatel y 70% oii the patients. Becausee L M W H remain the drug of first choice in pregnant women, both physiciann and patient have to be aware of these adverse effects. Introduction n Low-molecularr weight heparins (LMWH ) are widely used in patients in whom anticoagulantt therapy is indicated. Side effects include bleeding, hepari n induced thrombocytopenia ,, and hypersensitivit y reactions . Skin complications due to L M W HH use are considered to be rare, but their incidence is likely to be underreportedd ~. 1 hey vary from an urticarial rash (type I immediate hypersensitivityy reaction), to erythematous lesions (delayed type IV hypersensitivit y reaction)) and, exceptionally, skin necrosis. LMW HH are considered safe and effective in pregnant and lactatmg women In systemati cc reviews of L M W H use during pregnancy or the postpartum period, the reportedd incidences of generalise d skin reactions were low, i.e. 0.3% 0,6% . We reportt here a remarkabl y higher rate of skin complications.

A prospective cohort study on the absolute risks of venous thromboembolism and predictive value of screening asymptomatic relatives of patients with hereditary deficiencies of protein S, protein C or antithrombin

See also Keeling D. Thrombophilia screening or screaming. This issue, pp 1191–2.

Effects of recombinant activated factor VII on coagulation measured by thromboelastography in liver transplantation

Besides the conventional laboratory tests, thromboelastography (TEG) is used to monitor hemostasis during liver transplantation. A previous pilot study suggested a beneficial effect of recombinant activated factor VII (rFVIIa) on transfusion requirements in liver transplantation. In the present study, we assess the effects of rFVIIa on coagulation variables and TEG. In six study patients, the prothrombin time (PT), the activated partial thromboplastin time (aPTT) and TEG variables [reaction time (r), kinetic time (k), or clot formation time, α angle (α), and maximal amplitude (MA)] were recorded before and after the administration of a bolus of 80 μg/kg rFVIIa. These patients were compared with six controls who did not receive rFVIIa. In contrast with the control group, a significant shortening of PT (P = 0.028) and aPTT (P = 0.028), r (P = 0.046) and k (P = 0.043) values, and a significant incline of the α angle (P = 0.028) were noticed after injection of rFVIIa, whereas MA increased not significantly (P = 0.075). rFVIIa rapidly improved coagulation variables in liver transplant patients including PT and aPTT. Of the TEG variables, r, k and α angle significantly improved, and MA showed a trend to increase. These data suggest that rFVIIa not only influences the speed of clot formation, but also the physical properties of the clot, which cannot be detected by routine coagulation tests.

Total knee and hip arthroplasty in haemophilic patients

We evaluated the long‐term results of three total hip and nine total knee arthroplasties in nine haemophilic patients with disabling pain and end‐stage arthropathy. These patients have been followed over a period of 2–12u2003years (mean 6.9). One patient had a post‐operative haematoma, which was evacuated; two patients required manipulation of the knee because of a limited range of motion. There were no infections. At follow‐up, all but two patients were completely free of pain; two patients had occasional pain. The functional improvement was impressive with an average increase in the knee score from 37 to 80 points post‐operatively. The hip score increased from 36 to 85 points. The range of motion was increased in seven joints, unchanged in two joints and decreased in three. One total hip arthroplasty was revised after 9 years for aseptic loosening. One total knee demonstrated nonprogressive radiographic evidence of aseptic loosening. Median consumption of coagulation factor concentrate in severe haemophiliacs decreased from 47.00u2003Uu2003yr−1 (range 16.000–144.000) before surgery, to 25.000u2003Uu2003yr−1 (range 18.000–132.000) at 2u2003years after surgery. Conclusion: hip and knee arthroplasty is a valuable option in symptomatic haemophilic patients with disabling arthropathy, in order to obtain pain relief and functional improvement. It is associated with a low rate of complications and may reduce the need for substitution of factor VIII and IX.

Absolute risk of venous and arterial thrombosis in HIV-infected patients and effects of combination antiretroviral therapy

See also Lowe GDO. Arterial disease and venous thrombosis: are they related, and if so, what should we do about it? This issue, pp 1882-5; Agnelli G, Becattini C. Venous thromboembolism and atherosclerosis: common denominators or different diseases? This issue, pp 1886-90; Prandoni P, Ghirarduzzi A, Prins MH, Pengo V, Davidson BL, Sorensen H, Pesavento R, Iotti M, Casiglia E, Iliceto S, Pagnan A, Lensing AWA. Venous thromboembolism and the risk of subsequent symptomatic atherosclerosis. This issue, pp 1891-6; Eliasson angstrom, Bergqvist D, Bjorck M, Acosta S, Sternby NH, Ogren M. Incidence and risk of venous thromboembolism in patients with verified arterial thrombosis: a population study based on 23 796 consecutive autopsies. This issue, pp 1897-1902; van der Hagen PB, Folsom AR, Jenny NS, Heckbert SR, OMeara ES, Reich LM, Rosendaal FR, Cushman M. Subclinical atherosclerosis and the risk of future venous thrombosis in the Cardiovascular Health Study. This issue, pp 1903-8; Reich LM, Folsom AR, Key NS, Boland LL, Heckbert SR, Rosamond WD, Cushman M. Prospective study of subclinical atherosclerosis as a risk factor for venous thromboembolism. This issue, pp 1909-13; Ageno W, Prandoni P, Romualdi E, Ghirarduzzi A, Dentali F, Pesavento R, Crowther M and Venco A. The metabolic syndrome and the risk of venous thrombosis: a case-control study. This issue, pp 1914-8; S Young L, Ockelford P, Milne D, Rolfe-Vyson V, McKelvie S, Harper P. Post-treatment residual thrombus increases the risk of recurrent deep vein thrombosis and mortality. This issue, pp 1919-24; Squizzato A, Romualdi E, Ageno W. Why should statins prevent venous thromboembolism? A systematic literature search and a call for action. This issue, pp 1925-7.

Outcome of the subsequent pregnancy after a first loss in women with the factor V Leiden or prothrombin 20210A mutations

Summary.u2002 Background:u2002The factor V Leiden (FVL) and prothrombin 20210A (PTm) mutations are associated with single late pregnancy loss and recurrent early pregnancy loss. The prognosis after an initial loss in women with thrombophilia is uncertain. Objective:u2002To assess the pregnancy outcome of the second pregnancy after a first loss in women with and without either FVL or PTm mutations. Methods:u2002We selected women with a first pregnancy loss out of two family cohorts of first degree relatives of probands with FVL or PTm mutations and a history of documented venous thromboembolism or premature atherosclerosis. Results:u2002Ninety‐three women had had a first pregnancy loss and became pregnant a second time. Their risk of loss of the subsequent pregnancy was higher than in 825 women with a successful first pregnancy [25 vs. 12%, relative risk (RR) 2.0, 95% CI 1.4–3.0]. The live birth rate of the second pregnancy after an early first loss (≤u200312u2003weeks of gestation) was 77% (95% CI 62–87) for carriers and 76% (95% CI 57–89) for non‐carriers (RR 1.0, 95% CI 0.8–1.3). After a late first loss (>u200312u2003weeks), the live birth rates were 68% (95% CI 46–85) and 80% (95% CI 49–94) for carriers and non‐carriers, respectively (RR 0.9, 95% CI 0.5–1.3). Conclusions:u2002Women with a first pregnancy loss have a 2‐fold increased risk of loss of the subsequent pregnancy, regardless of their carrier status. More importantly, the outcome of the second pregnancy is rather favorable in absolute terms, even for those with thrombophilia and a late loss, which raises concern regarding the risks and presumed benefits of anticoagulant therapy in these women.